Pharmacodynamic characterization and evaluation of oxidative stress effects of digitoxigenin derivatives on HeLa cells.

Cancer is a leading cause of death worldwide and its treatment is hampered by the lack of specificity and side effects of current drugs. Cardiotonic steroids (CTS) interact with Na/K-ATPase (NKA) and induce antineoplastic effects, but their narrow therapeutic window is key limiting factor. The synthesis of digitoxigenin derivatives with glycosidic unit modifications is a promising approach to develop more selective and effective antitumor agents.

Simplified Method for Kinetic and Thermodynamic Screening of Cardiotonic Steroids through the K-Dependent Phosphatase Activity of Na/K-ATPase with Chromogenic pNPP Substrate.

The antitumor effect of cardiotonic steroids (CTS) has stimulated the search for new methods to evaluate both kinetic and thermodynamic aspects of their binding to Na/K-ATPase (IUBMB Enzyme Nomenclature). We propose a real-time assay based on a chromogenic substrate for phosphatase activity (pNPPase activity), using only two concentrations with an inhibitory progression curve, to obtain the association rate ( ), dissociation rate ( ), and equilibrium ( ) constants of CTS for the structure-kinetics relationship in drug screening. We show that changing conditions (from ATPase to pNPPase activity) resulted in an increase of of the cardenolides digitoxigenin, essentially due to a reduction of In contrast, the of the structurally related bufadienolide bufalin increased much less due to the reduction of its partially compensating the decrease of its When evaluating the kinetics of 15 natural and semisynthetic CTS, we observed that both and correlated with (Spearman test), suggesting that differences in potency depend on variations of both and A rhamnose in C3 of the steroidal nucleus enhanced the inhibitory potency by a reduction of rather than an increase of Raising the temperature did not alter the of digitoxin, generating a ΔH ( ) of -10.

Internal and external adenomyosis phenotypes: ultrasound features and association with clinical outcomes.

Study Question: What are the sonographic and clinical findings in women diagnosed with external and internal adenomyosis by ultrasound?

Summary Answer: Patients with external and internal adenomyosis phenotypes, diagnosed by ultrasound, present differences in sonographic features of the disease and demographic characteristics including age, parity, and association with deep endometriosis (DE) and leiomyomas.

What Is Known Already: Two different phenotypes of adenomyosis have been described based on the anatomical location of adenomyotic lesions in the myometrium, suggesting that adenomyosis affecting the inner myometrium and that affecting the external myometrial layer may have distinct origins.

Study Design, Size, Duration: A cross-sectional study including 505 patients with a sonographic diagnosis of adenomyosis was performed between January 2021 and December 2022.

Comparative analysis of endometrial, vaginal, and gut microbiota in patients with and without adenomyosis.

Introduction: Alterations in microbiota composition have been implicated in a variety of human diseases. Patients with adenomyosis present immune dysregulation leading to a persistent chronic inflammatory response. In this context, the hypothesis that alterations in the microbiota may be involved in the pathogenesis of adenomyosis, by affecting the epigenetic, immunologic, and biochemical functions of the host, has recently been postulated.

Evaluation of menstrual symptoms after Coronavirus disease 2019 vaccination in women with endometriosis.

Background: Vaccination can have an impact on menstruation, and this impact may be more notable in women with inflammatory gynecological pathologies such as endometriosis.

Objectives: We aimed to investigate the impact of mRNA-based SARS-CoV-2 vaccines on menstrual cycle-related symptoms in women with endometriosis and assess the effect of hormonal therapy on potential SARS-CoV-2 vaccination-induced menstrual changes.

Design: A total of 848 women who received at least two doses of mRNA-based COVID-19 vaccines were prospectively recruited: 407 with endometriosis (endometriosis group) and 441 healthy controls (non-endometriosis group).